[7440-66-6] · Zn · Zinc/Silver Couple · (MW 65.39)
(dehalogenation; preparation of organozinc compounds for carbon-carbon bond formation; cyclopropanations)
Physical Data: Zn: mp 419.5 °C; d 7.140 g cm-3.
Solubility: insol most solvents. The reactions are typically run as suspensions with THF as solvent for preparation of organozinc reagents and MeOH utilized for most of the reductions. Et2O, DMSO, and DMA have also been used as solvents.
Preparative Methods: Zinc powder (100 g) is added all at once to a refluxing solution of Silver(I) Acetate (100 mg) in 200 mL of acetic acid. The mixture is stirred for 30 s and quickly cooled. The zinc/silver couple is isolated by decantation and washed with anhydrous ether (6 × 100 mL), dried under vacuum, and stored at room temperature.1 An alternative method uses zinc dust that has been prewashed with 10% HCl and uses a slightly higher Ag to Zn ratio.2
Handling, Storage, and Precautions: Zn is a moisture-sensitive, flammable solid. The Zn/Ag couple appears to be stable for months at room temperature if stored under an inert atmosphere.
The Zn/Ag couple is a very effective reducing agent for carbon-halogen bonds. It has been used to dehalogenate b-chloro-a,b-unsaturated ketones in good yield (eqs 1 and 2).2,3
Aldehydes and ketones can be protected as their 5,5-dibromo-1,3-dioxane derivatives by reaction with 2,2-dibromo-1,3-propanediol. This carbonyl protecting group introduces no new chirality and is stable to a number of reagents that would normally react with the carbonyl. These derivatives can be deprotected under neutral conditions using Zn/Ag couple (eq 3).4
The debromination of 1,2-dibromides to form the corresponding alkene can be accomplished with Zn/Ag couple, as shown for the preparation of the Dewar benzene derivative (eq 4).5
The final steps in the synthesis of one of the tricothecenes required the alkene and hydroxymethyl group to be simultaneously protected as the intramolecular bromo ether. The unraveling of the bromo ether was accomplished using Zn/Ag couple (eq 5).6
Zn/Ag couple has been utilized to debrominate selectively the bromohydrin penicillinate (eq 6). This produces a mixture of diastereomers in the ratio indicated.7
Reduction of the a-bromoacylphosphate produces the intermediate ketene which undergoes cycloaddition to produce the cyclobutanedione (eq 7). Attempts to prepare the acid chloride to use in place of the phosphate failed.8
Zn/Ag couple is an effective alternative to the commonly employed Zinc/Copper Couple couple in the Simmons-Smith reaction. It is reportedly superior for cyclopropanations of a,b-unsaturated carbonyl compounds, conjugated alkenes, and alkenes derived from ketones (enol derivatives) because of increased reactivity, better yields, and short reaction times (eqs 8 and 9).9
The use of the Zn/Ag couple has been suggested for the large scale [4 + 3] cycloaddition of a,a,a´,a´-tetrabromoacetone and furan. The yield is lower than the iron carbonyl promoted reaction but has advantages in terms of economics and operational simplicity (eq 10).10
The synthesis of b,g-unsaturated ketones from nitriles and allylic bromides has been improved by employing the Zn/Ag couple. The method is simple and provides the ketones in good to excellent yield. The use of crotyl or isopropenyl bromides results in the formation of the products from g-attack (eq 11). The reactions can be run in ether, benzene, or THF. The use of THF tends to suppress Wurtz couplings.1
(Trimethylsilylmethyl)difluorochloropropene regioselectively couples with carbonyl compounds to afford 2,2-difluoro-3-[(trimethylsilyl)methyl]-3-butenols in good yield (eq 12).11
In a synthesis of steganone, the diketo dibromide was intramolecularly cyclized utilizing Zn/Ag couple (eq 13).12
Zn/Ag couple is an effective reagent for use in the Reformatsky reaction. If bromocrotonates are employed, there is the possibility of either a- or g-attack. In the case of the crotonates, unlike the allylic halides, the product is dependent on the choice of solvent. When ether is used, the products arise from a-attack, while products derived from g-attack are formed if THF is used (eq 14).13
An intramolecular version of the Blaise reaction was employed in the synthesis of corynantheine alkaloids. This variant of the Blaise reaction utilized Zn/Ag couple and ultrasonic irradiation (eq 15). The use of other forms of activated Zn or the omission of ultrasound resulted in poor or nonexistent yields of products.14
The use of ultrasound also resulted in an increase in yield for a Zn/Ag mediated coupling of the allylic bromide of the dihydrothiophene S,S-dioxide (eq 16).15
Michael J. Taschner
The University of Akron, OH, USA